Primary cilia function as critical sensory organelles that mediate multiple signaling pathways, including the Hedgehog (Hh) pathway, which is essential for organ patterning and morphogenesis. Disruptions in Hh signaling have been implicated in supernumerary tooth formation and molar fusion in mutant mice. Cilk1, a highly conserved serine/threonine-protein kinase localized within primary cilia, plays a critical role in ciliary transport. Loss of Cilk1 results in severe ciliopathy phenotypes, including polydactyly, edema, and cleft palate. However, the role of Cilk1 in tooth development remains unexplored. In this study, we investigated the role of Cilk1 in tooth development. Cilk1 was found to be expressed in both the epithelial and mesenchymal compartments of developing molars. Cilk1 deficiency resulted in altered ciliary dynamics, characterized by reduced frequency and increased length, accompanied by downregulation of Hh target genes, such as Ptch1 and Sostdc1, leading to the formation of diastemal supernumerary teeth. Furthermore, in Cilk1^-/-;PCS1-MRCS1^△/△ mice, which exhibit a compounded suppression of Hh signaling, we uncovered a novel phenomenon: diastemal supernumerary teeth can be larger than first molars. Based on these findings, we propose a progressive model linking Hh signaling levels to sequential changes in tooth patterning: initially inducing diastemal supernumerary teeth, then enlarging them, and ultimately leading to molar fusion. This study reveals a previously unrecognized role of Cilk1 in controlling tooth morphology via Hh signaling and highlights how Hh signaling levels shape tooth patterning in a gradient-dependent manner.
Animals ; Hedgehog Proteins/physiology* ; Mice ; Signal Transduction/physiology* ; Tooth, Supernumerary ; Molar ; Cilia/physiology* ; Odontogenesis/physiology* ; Patched-1 Receptor ; Protein Serine-Threonine Kinases/physiology* ; Mice, Knockout ; Adaptor Proteins, Signal Transducing

Background: While polystyrene microplastics (PS-MPs) are emerging as potentially significant health threats, linked to cancer and reproductive dysfunction, their precise effects on human health remain largely unknown. We aimed to investigate the underlying mechanisms promoting microplastic-induced damage in the reproductive system. Methods: Thirty C57BL/6 male mice were randomly allocated into six equal-sized groups.Mice were exposed to fluorescent PS-MPs (5 µm, < 18%, green) at a dose of 1 and 3 mg/dL via oral gavage for 28 and 56 days, respectively (control, 0 mg/dL). The presence of antibodies and inflammatory and oxidative stress markers were evaluated using western blotting. Sperm analysis was also performed. Mouse testis Sertoli TM4 cells were divided into two groups:control (medium only) and PS-MPs (medium containing, 1,000 μg/mL) groups and cultured in vitro for 1, 24, 48, or 72 hours. The cells were cultured in a Ham’s F12: Dulbecco's Modified Eagle Medium medium with 0.25% fetal bovine serum at 37°C with humidified atmosphere of 5% carbon dioxide in the air. Protein analyses for interleukin (IL)-6, IL-10, NADPH-oxidase (NOX)-2, NOX-4, hypoxia-inducible transcription factor (HIF)-2α, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β were performed using western blotting. Results: The testes were evaluated after 28 and 56 days of exposure. Varying sizes of PS-MPs were detected in the testes (ranging from 5.870 to 7.768 µm). Significant differences in sperm concentration, motility, and the proportion of normal sperm were observed between the two groups. An increase in TGF-β, HIF-2α, and NOX-4 levels was observed using western blot analysis. However, no dose-dependent correlations were observed between the two groups.In vitro evaluation of the PS-MPs group displayed PS-MP penetration of the lumen of Sertoli cells after 1 hour. Further PS-MP aggregation within Sertoli cells was observed at 24, 48, and 72 hours. A significant increase in inflammatory protein expressions (IL-10, TGF-β, MCP-1, IL-6, TNF-α, and HIF-2α) was observed through western blotting, although oxidative agents did not show a significant increase. Conclusion PS-MPs induced reproductive dysfunction in male mice provide new insights into PS-MPs-associated toxicity in mammals.

Kaposi’s varicelliform eruption (KVE) is a rare viral infection primarily caused by herpes simplex virus (HSV). This condition frequently presents concomitantly with underlying chronic skin disorders, particularly atopic dermatitis (AD). This report describes a rare case of sepsis resulting from KVE in a patient with AD. A 30-year-old male patient with a history of AD presented with painful skin lesions characterized by papulovesicular eruptions, crusts, erythema, and erosions, initially localized to the neck and spreading throughout his body, accompanied by a high fever. Laboratory findings confirmed HSV infection and sepsis. Thus, a diagnosis of KVE compounded by sepsis was established. Systemic acyclovir and antibiotics led to complete recovery within 3 weeks, with resolution of fever and skin manifestations, and general health improvement. Timely recognition and management of KVE are crucial for prevention of adverse outcomes. Both physicians and patients with AD should be made aware of the predisposing factors and risks associated with KVE.

Congenital smooth muscle hamartoma is a benign proliferation of smooth muscles within the dermis. The classic form presents as well-defined, skin-colored, or hyperpigmented plaques associated with hypertrichosis. However, there have been reports of atypical forms, including a follicular spotted appearance, linear atrophic plaques, and morphea-like forms. In such cases, distinguishing congenital smooth muscle hamartomas from other cutaneous diseases can be challenging. Herein, we report on a 16-month-old boy who presented with a hypopigmented patch and hypertrichosis on his back since birth. Histopathological examination revealed mild acanthosis and well-defined smooth muscle bundles haphazardly oriented in the dermis. These bundles stained positively with Masson’s trichrome stain. Based on these findings, a definitive diagnosis of congenital smooth muscle hamartoma was established. In conclusion, an exceptionally rare case of congenital smooth muscle hamartoma with a hypopigmented appearance is reported.

Background: Female-pattern hair loss (FPHL) is characterized by diffuse hair thinning in the mid-frontal scalp and increased hair shedding. Although the use of low-dose oral minoxidil (LDOM) is increasing significantly in Korea, data on its use are limited. Objective: To determine the efficacy and safety of LDOM in Korean patients with FPHL. Methods: This retrospective, single-center study was conducted at Pusan National University Hospital. The study included female patients with pattern hair loss who received treatment with LDOM at 1.25 mg/d for a minimum of 6 months in combination with other treatments. Patients were eligible for LDOM addition if their previous treatments showed a limited response and the previous treatment regimen remained unchanged throughout the evaluation period. Clinical response to treatment was evaluated using the Sinclair hair loss severity scale. Results: The study included 44 females with FPHL. Before treatment, the mean Sinclair scale score was 2.77, which decreased to 2.27 after treatment. By the 3rd month, one patient (2.3%) experienced worsening, while seven patients (15.9%) showed slight improvement. By the 6th month, the treatment response was as follows: stabilization in 30 patients (68.2%), slight improvement in 13 patients (29.5%), and substantial improvement in one patient (2.3%). Adverse effects, predominantly hypertrichosis, were observed in nine patients. All adverse effects improved upon discontinuation of LDOM and no life-threatening adverse effects were observed during the study. Conclusion This study provides evidence that LDOM can be an effective therapeutic option with a good safety profile for FPHL.

Background: Daily usage of facial masks during coronavirus disease 2019 pandemic influenced on facial dermatoses. Objective: This study investigated the impact of mask-wearing habits on facial dermatoses. Methods: A nationwide, observational, questionnaire-based survey was conducted from July through August 2021, involving 20 hospitals in Korea. Results: Among 1,958 facial dermatoses, 75.9% of patients experienced aggravation or development of new-onset facial dermatoses after wearing masks. In aggravated or newly developed acne patients (543 out of 743), associated factors were healthcare provider, female gender, and a long duration of mask-wearing. Irritating symptoms, xerosis, and hyperpigmentation were more frequently observed in this group. Aggravated or newly developed rosacea patients (515 out of 660) were likely to be female, young, and have a long duration of mask-wearing per day. Seborrheic dermatitis patients who experienced aggravation or de novo development (132 out of 184) were younger, and they more frequently involved the chin and jaw in addition to the nasolabial folds and both cheeks. Contact dermatitis patients (132 out of 147) with aggravation or de novo development tended to be female, involve both cheeks, and complain of pruritus. Aggravated or newly developed atopic dermatitis patients (165 out of 224) were more likely to be female, and had a higher baseline investigator global assessment score before mask-wearing. Conclusion Clinical features and factors related to aggravation were different according to the types of facial dermatoses.

Background: More than half of acne patients have truncal acne on their chest, back, and shoulders. However, since most studies on acne have focused on the face, data on clinical characteristics and proper management for truncal acne are insufficient. Objective: To establish a Korean Acne Rosacea Society (KARS) consensus for experts’ perception and treatment patterns of truncal acne. Methods: We conducted two rounds of the Dephi technique to gather expert opinion and reach a consensus on truncal acne. The first round comprised 48 questionnaires focusing on various aspects such as epidemiology, clinical features, diagnosis, treatment, prognosis and more, while second rounds consisted of 26 questionnaires. Results: A total of 36 dermatologists (36/38 KARS members, 94.7%) completed this survey. In the first-round survey, consensus was reached on 20 out of the 48 questions (41.7%). In the secondround questionnaire, consensus was achieved on 9 of the 26 questions (34.6%). The most unresponsive lesion to truncal acne treatment was scars (atrophic/hypertrophic). The most commonly used treatments for each non-inflammatory and inflammatory truncal acne lesions were selected to use topical retinoids (78.1% of the responders) and oral antibiotics (93.8% of the responders). Conclusion Our study has yielded valuable insights into the epidemiology, clinical manifestations, diagnosis, treatment, and quality of life of patients with truncal acne. We anticipate that this study will inspire further comprehensive research for individuals with truncal acne.

Background: and PurposePeripheral neuropathies (PNs) are a common but poorly understood complication of chronic obstructive pulmonary disease (COPD). To clarify the initial trigger of a PN in COPD, we investigated the excitability of peripheral nerves in patients with COPD. Methods: The automated nerve excitability test (NET) using the threshold-tracking paradigm was applied to 20 COPD patients. The recording protocol calculated the strength–duration time constant, threshold electrotonus (TE), current–threshold relationship, and recovery cycle (RC). Each NET parameter was compared with two control groups: normal controls group (NC group) and smokers without COPD group (smoker group). Results: In the motor NETs, the change in the threshold in the mid-depolarizing phase of TE (40–60 ms) was smaller in the COPD group (50.7%±1.2%, mean±SEM; n=20) than in the NC group (54.5%±0.7%, n=25; p<0.01), as was the prominence of superexcitability in the RC (-22.6%±1.5% and -26.4%±1.1%, respectively; p=0.04). There were no significant differences in the sensory NETs. Comparisons between the COPD and smoker groups (n=25) also showed no differences in either the motor or sensory NETs. Conclusions The pattern of excitability in COPD revealed a membrane depolarization attributable to Na+–K+–ATPase failure in the axolemma of distal motor nerves. This finding suggests that chronic hypoxemia and adaptative process can alter axonal excitability and trigger a resultant neuropathic process that is antecedent to PN in COPD.

The survival rate of children admitted in the neonatal intensive care unit (NICU) after birth is on the increase; hence, proper evaluation and care of their neurodevelopment has become an important issue. Neurodevelopmental assessments of individual domains regarding motor, language, cognition, and sensory perception are crucial in planning prompt interventions for neonates requiring immediate support and rehabilitation treatment. These assessments are essential for identifying areas of weakness and designing targeted interventions to improve future functional outcomes and the quality of lives for both the infants and their families. However, initial stratification of risk to select those who are in danger of neurodevelopmental disorders is also important in terms of cost-effectiveness. Efficient and robust functional evaluations to recognize early signs of developmental disorders will help NICU graduates receive interventions and enhance functional capabilities if needed. Several age-dependent, domain-specific neurodevelopmental assessment tools are available; therefore, this review summarizes the characteristics of these tools and aims to develop multidimensional, standardized, and regular follow-up plans for NICU graduates in Korea.